Glucocorticoids exert a variety of actions on various tissues and organs. These hormones act in a concert with other hormones in a permissive way. In addition, these hormones are widely used as therapeutics for inflammatory and immunological diseases; this is based upon their anti-inflammatory and immunosuppressive actions. We recently isolated lipocortin, a phospholipase inhibitory protein, from the media conditioned with glucocorticoid-treated U937 cells (a human monocyte cell line) and glucocorticoid-treated human peripheral leukocytes. Highly purified preparations of lipocortin can inhibit phospholipase A2 in vitro and inhibit chemotaxis of leukocytes in situ, suggesting that anti-inflammatory activity of glucocorticoids is mediated through this protein. Since these preparations also alter the glycolysis in rat hepatocytes mediated through Alpha- and Beta-adrenergic receptors, lipocortin is also suggested to be involved in the signal transduction of these receptors. These observations implicate that lipomodulin might mimic some of the permissive effects of glucocorticoids.